Thiazolidinone-Related Heterocyclic Compounds as Potential Antitrypanosomal Agents

Human African trypanosomiasis (HAT) and Chagas disease are neglected tropical diseases (NTDs) due to parasite protists from the Trypanosoma genus transmitted by insect vectors. Trypanosomiases affect mostly poor populations in the developing countries, and the development of new antitrypanosomal drugs is underinvested by governments and the pharmaceutical industry. In this chapter, we described the development of 4-thiazolidinone and thiazole derivatives with heterocyclic fragments which exhibit good inhibition of trypanosome growth and might constitute potential candidates for the development of new drugs against trypanosomiasis. Antitrypanosomal design, mainly within structure-based design, led to the synthesis of 5-ene-4-thiazolidinone-3-alkanecarboxylic acids; 2,3-disubstituted 4-thiazolidinones; thiazolidinone-pyrazoline, phenylindole-thiazolidinone, and imidazothiadiazole-thiazolidinone hybrids; as well as 4-thiazolidinone-based fused heterocycles, especially thiopyrano[2,3-d]thiazoles, and non-thiazolidinone compounds–namely, isothiocoumarine derivatives. Moreover, antitrypanosomal 4-thiazolidinones are of special interest in the search for new antimalarial and antileishmanial agents. Also many active anticancer agents among the abovementioned 4-thiazolidinones have been discovered

The native form of thePlasmodium falciparum Pf68 neutral proteinase is a 105,000-Da polypeptide

International audienc

Probiotics for the Control of Parasites: An Overview

Probiotics are defined as live organisms, which confer benefits to the host. Their efficiency was demonstrated for the treatment of gastrointestinal disorders, respiratory infections, and allergic symptoms, but their use is mostly limited to bacterial and viral diseases. During the last decade, probiotics as means for the control of parasite infections were reported covering mainly intestinal diseases but also some nongut infections, that are all of human and veterinary importance. In most cases, evidence for a beneficial effect was obtained by studies using animal models. In a few cases, cellular interactions between probiotics and pathogens or relevant host cells were also investigated using in vitro culture systems. However, molecular mechanisms mediating the beneficial effects are as yet poorly understood. These studies indicate that probiotics might indeed provide a strain-specific protection against parasites, probably through multiple mechanisms. But more unravelling studies are needed to justify probiotic utilisation in therapeutics

CO2 leakage in a shallow aquifer - Observed changes in case of small release

International audienceGeological storage of CO2 in deep saline aquifers is one of the options considered for the mitigation of CO2 emissions into the atmosphere. A deep geological CO2 storage is not expected to leak but potential leakage monitoring is required by legislation, as e.g. the EU Directive relative to Geological Storage of CO2. To ensure that the storage will be permanent and safe for the environment and human health, the legislation require that the CCS operators monitor the injection, the storage complex and if needed the environment to detect any CO2 leakage and its hazardous effects on the environment. Various monitoring methods are available for the monitoring of CO2 storage sites and the environment as listed by the IEA-GHG and the monitoring selection tool. Geophysical based methods have a greater area of investigation but may suffer from insufficient sensitivities to detect small leakages. At the opposite, geochemical monitoring methods may have insufficient investigation area but may be able to detect more subtle changes even if monitoring in deep environments is not straightforward. Leakage detection is not yet well constrained and research efforts and tests are required to gain confidence into monitoring strategies. In the framework of the CIPRES project, funded by the French Research Agency, a shallow CO2 release experiment has been performed in October 2013 in a chalk aquifer from the Paris basin. The Catenoy site has been characterised since March 2013 through several wells set on a straight line oriented along the local flow (see Gombert et al., this conference). Such an experiment is designed to gain confidence in leakage detection in subsurface environments by understanding processes and principles governing seepage occurrence. Contrary to other experiments such as ZERT or CO2FieldLab ones, where gaseous CO2 was injected directly in the water, the injection was done with water saturated with CO2 at atmospheric pressure. 10 m3 of water were pumped from the aquifer, then saturated with 20 kg of food-grade CO2 and injected during 40 hours between 12 and 25 m depth. Daily monitoring of soil gases and water was performed during injection and post-injection phases (2 weeks duration) in the area previously delimited by a tracer test. The aim is to determine if geochemical methods are accurate enough to allow detecting small release in shallow environments. If successful, such an experiment can help to gain confidence in leakage detection. As expected, no change was noticed in the unsaturated zone. The shape of gas concentrations distribution at the surface (CO2, O2, N2, 4He, 222Rn) observed during the injection is strictly similar to the repartition of gas species observed since March 2013. The main process observed is respiration and no change linked to the injection was highlighted, only seasonal effects. Slight changes were observed in the saturated zone. The water was collected at 15 m deep excepted for one stratified borehole where water was sampled at 15 and 18 m. The pH of the injected water was lower (mean value: 5.3±0.1) than the initial pH of the aquifer (7.1-7.2) due to CO2 dissolution. Only two monitoring boreholes set 10 m and 20 m downstream from the injection well may be considered as influenced by the experiment. A probable enrichment in HCO3 linked to interaction of the CO2 saturated water with chalk was noticed, with an enrichment close to +8 to +10% of the initial value. For one borehole the pH value remained nearly stable in relation with pH buffering and in the other borehole a slight decrease was observed (-0.1 to -0.15 pH unit). However this decrease is significant as it is above the instrumental uncertainty of the electrodes. In addition, a slight increase of the electrical conductivity was noticed but it did not exceed +6% compared to baseline data. Such slight changes in the physico-chemical parameters are related to small variations in dissolved elements. Apart from HCO3, the other major ion affected by CO2-water rock-interaction is Ca as the aquifer is mainly composed by calcite. Concentrations increases by +8 to +9% whose amplitude is in agreement with the increase of HCO3. Trace elements were also little affected, the main change concerned Sr (+8 to +10% increase). Modifications occurring during this CO2 release experiment have small amplitude as expected but these results highlight that geochemical methods are able to detect small leakages. Consequently, effects were noticed only during a short period of time. It is not possible to determine if all the injected CO2 has migrated downwards in the direction of flow or if partial lateral migration has occurred, but post-injection monitoring and boreholes logging 12 days after the stop of injection did not reveal any discrepancy in the water columns. On the other hand, the magnitude of the pH change is consistent with the behaviour of the co-injected tracer (dilution ratio ~30). In the perspective of getting more information on the remobilisation of trace metal elements, a push-pull test will be performed in 2014 on the basis of the learning of this first experiment

CO2 leakage in a shallow aquifer – Observed changes in case of small release

AbstractGeological storage of CO2 in deep saline aquifers is one of the options considered for the mitigation of CO2 emissions into the atmosphere. A deep geological CO2 storage is not expected to leak but potential leakage monitoring is required by legislation, as e.g. the EU Directive relative to Geological Storage of CO2. To ensure that the storage will be permanent and safe for the environment and human health, the legislation require that the CCS operators monitor the injection, the storage complex and if needed the environment to detect any CO2 leakage and its hazardous effects on the environment. Various monitoring methods are available for the monitoring of CO2 storage sites and the environment as listed by the IEA-GHG and the monitoring selection tool. Geophysical based methods have a greater area of investigation but may suffer from insufficient sensitivities to detect small leakages. At the opposite, geochemical monitoring methods may have insufficient investigation area but may be able to detect more subtle changes even if monitoring in deep environments is not straightforward. Leakage detection is not yet well constrained and research efforts and tests are required to gain confidence into monitoring strategies.In the framework of the CIPRES project, funded by the French Research Agency, a shallow CO2 release experiment has been performed in October 2013 in a chalk aquifer from the Paris basin. The Catenoy site has been characterised since March 2013 through several wells set on a straight line oriented along the local flow (see Gombert et al., this conference). Such an experiment is designed to gain confidence in leakage detection in subsurface environments by understanding processes and principles governing seepage occurrence. Contrary to other experiments such as ZER

Antileishmanial and trypanocidal activity of brazilian Cerrado plants

The side effects and the emerging resistance to the available drugs against leishmaniasis and trypanosomiasis led to the urgent need for new therapeutic agents against these diseases. Thirty one extracts of thirteen medicinal plants from the Brazilian Cerrado were therefore evaluated in vitro for their antiprotozoal activity against promastigotes of Leishmania donovani, and amastigotes of Trypanosoma cruzi. Among the selected plants, Casearia sylvestris var. lingua was the most active against both L. donovani and T. cruzi. Fifteen extracts were active against promastigotes of L. donovani with concentrations inhibiting 50% of parasite growth (IC50) between 0.1-10 µg/ml, particularly those of Annona crassiflora (Annonaceae), Himatanthus obovatus (Apocynaceae), Guarea kunthiana (Meliaceae), Cupania vernalis (Sapindaceae), and Serjania lethalis (Sapindaceae). With regard to amastigotes of T. cruzi, extracts of A. crassiflora, Duguetia furfuracea (Annonaceae), and C. sylvestris var. lingua were active with IC50 values between 0.3-10 µg/ml. Bioassay fractionations of the more active extracts are under progress to identify the active antiparasite compounds